Dysregulation of estrogen signaling and HSD17B7 in the prostate stroma of African American men.

African American men experience a higher incidence and severity of prostate cancer relative to European American men, and there is a range of risk factors that may contribute to this disparity. Prostate adenocarcinoma originates from the epithelium, which is significantly influenced by signaling from the surrounding fibromuscular stroma. To identify ancestry-associated differences in the stroma, gene expression profiling was compared between laser-capture microdissected prostate cancer stroma from patients of African descent and those of European descent. Estrogen receptor signaling was the top differential pathway between the groups, with the steroid hormone dehydrogenase HSD17B7 identified as the most differentially expressed gene. In a separate cohort of patients, protein expression of HSD17B7 was higher in African American patients relative to European American patients in a radical prostatectomy tissue microarray, validating the transcriptional findings. African American patients also exhibited significantly increased levels of HSD17B7 protein in the stroma surrounding benign areas compared to the stroma near tumors. These studies provide important evidence of ancestry-associated differences in stromal estrogen signaling.